TOXINS AND ANTITOXINS 61 



fatal dose of toxin into the hind legs of guinea-pigs and seventeen 

 to twenty-four hours subsequently injected antitoxin by various 

 routes. Six animals receiving the immune serum subcutaneously 

 died ; fifteen received it intracardially and two survived, whereas 

 sixteen animals received it intrathecally and thirteen survived. It 

 was found that the dose necessary for intrathecal injection was con- 

 siderably smaller than the dose necessary for injection into the cir- 

 culation. Sherrington conducted a similar series of experiments 

 upon monkeys with essentially the same results. He used twenty- 

 five monkeys for his series of injections and the following table 

 gives the results : 



Time between 



Route of injection giving of toxin Recoveries Deaths 



and antitoxin 



Lumbar intrathecal 47-78 hours 14 1 1 



Bulbar intrathecal 47-78 hours 13 12 



Intravenous 47~78 hours 7 18 



Intramuscular 47-78 hours 3 22 



Subcutaneous 47-78 hours 2 23 



Cerebral subdural, ten cases 47~78 hours o 10 



Clinically Irons was not able to demonstrate such a marked dif- 

 ference in results, and Leishman and Smallman came to the conclu- 

 sion that the intramuscular route is the best. The work of Andrew 

 and Golla demonstrated the clinical value of the intrathecal method. 

 Experimental work also shows that although antitoxin can take up 

 toxin after fixation with nerve tissue, such a release of toxin is re- 

 stricted by long contact with the nerve tissue. This explains the 

 necessity for early administration of antitoxin. For example, the 

 experiments of Doenitz show that the amount of antitoxin neces- 

 sary for protection increases tremendously with a lapse of time. 

 He injected twelve times the fatal doses of toxin and found that 

 after the lapse of four minutes a slight excess of antitoxin was suffi- 

 cient to protect the animal, but after eight minutes six times this 

 dose of antitoxin was required ; after sixteen minutes twelve times 

 the dose, after 1 hour twenty-four times the dose; in four to six 

 hours six hundred times the original dose, and after six hours he 

 was unable to save the animals. As a result of long experience with 

 treatment it has finally been determined that a combination of 

 modes of injection is desirable in order to procure complete and 

 lasting saturation of the body with antitoxin. When giving intra- 

 thecal injections it is well to draw off the spinal fluid and then 

 immediately inject 3000 to 5000 units of toxin, diluting the serum 

 to a volume of 10 to 15 c.c. with sterile salt solution. Where no 

 fluid can be withdrawn from the spinal canal the antitoxin is intro- 

 duced very slowly by gravity. The intrathecal injection is further 

 supplemented by 10,000 to 15,000 units intravenously, and three to 

 four days later a similar injection subcutaneously. It is often ad- 

 visable to repeat the intrathecal injections each day for three or 

 four days. The following outline taken from the Memorandum 



